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https://www.readbyqxmd.com/read/28069454/c1473g-polymorphism-in-mouse-tryptophan-hydroxylase-2-gene-in-the-regulation-of-the-reaction-to-emotional-stress
#1
Ekaterina Y Bazhenova, Daria V Bazovkina, Elizabeth A Kulikova, Dariya V Fursenko, Nikita V Khotskin, Daria V Lichman, Alexander V Kulikov
Neurotransmitter serotonin (5-HT) is involved in the regulation of stress response. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of serotonin (5-HT) synthesis in the brain. C1473G polymorphism in Tph2 gene is the main factor defining the enzyme activity in the brain of laboratory mice. The effect of interaction between C1473G polymorphism and 30min restriction stress on the behavior in the open field test, c-Fos gene expression and 5-HT metabolism in the brain in adult male of B6-1473C and B6-1473G congenic mouse lines with high and low TPH2 activity was investigated...
January 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28068779/norepinephrine-transporter-gene-variants-and-remission-from-depression-with-venlafaxine-treatment-in-older-adults
#2
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
January 10, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28029782/a-tph2-gfp-reporter-stem-cell-line-to-model-in-vitro-and-in-vivo-serotonergic-neuron-development-and-function
#3
Giulia Pacini, Attilio Marino, Sara Migliarini, Elisa Brilli, Barbara Pelosi, Giacomo Maddaloni, Marta Pratelli, Mario Pellegrino, Aldo Ferrari, Massimo Pasqualetti
Modeling biological systems in vitro has contributed to clarify complex mechanisms in simplified and controlled experimental conditions. Mouse embryonic stem (mES) cells can be successfully differentiated towards specific neuronal cell fates, thus representing an attractive tool to dissect, in vitro, mechanisms that underlie complex neuronal features. In this study, we generated and characterized a reporter mES cell line, called Tph2(GFP), in which the vital reporter GFP replaces the Tryptophan hydroxylase 2 (Tph2) gene...
December 28, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28012347/enhanced-dendritic-morphogenesis-of-adult-hippocampal-newborn-neurons-in-central-5-ht-deficient-mice
#4
Ning-Ning Song, Qiong Zhang, Ying Huang, Ling Chen, Yu-Qiang Ding, Lei Zhang
Serotonin (5-HT) plays an important role in regulating adult hippocampal neurogenesis. Chronic administration of selective 5-HT reuptake inhibitors (SSRIs), which up-regulates extracellular 5-HT concentration, accelerates the maturation of adult-born hippocampal neurons. It is unknown, however, about effects of central 5-HT-deficiency on the dendritic morphogenesis of these newborn neurons. Here, we address this question using two central 5-HT-deficient mouse models, Tph2 conditional knockout mice (CKO) losing central 5-HT from embryonic stage, and Pet1-Cre;Rosa26-DTR (diphtheria toxin receptor) mice lacking central 5-HT neurons exclusively in adulthood...
December 15, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/28008302/benefits-of-hormone-therapy-estrogens-depend-on-estrogen-type-17%C3%AE-estradiol-and-conjugated-equine-estrogens-have-differential-effects-on-cognitive-anxiety-like-and-depressive-like-behaviors-and-increase-tryptophan-hydroxylase-2-mrna-levels-in-dorsal-raphe-nucleus
#5
Ryoko Hiroi, Giulia Weyrich, Stephanie V Koebele, Sarah E Mennenga, Joshua S Talboom, Lauren T Hewitt, Courtney N Lavery, Perla Mendoza, Ambra Jordan, Heather A Bimonte-Nelson
Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related disorders. In particular, polymorphisms of tryptophan hydroxylase-2 (TpH2, the brain-specific, rate-limiting enzyme for 5-HT biosynthesis) are implicated in cognitive and affective disorders...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27989490/paraphilic-sexual-offenders-do-not-differ-from-control-subjects-with-respect-to-dopamine-and-serotonin-related-genetic-polymorphisms
#6
Andrzej Jakubczyk, Aleksandra Krasowska, Marcin Bugaj, Maciej Kopera, Anna Klimkiewicz, Agata Łoczewska, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Anna Podgórska, Małgorzata Sołowiej, Leszek Markuszewski, Sławomir Jakima, Rafał Płoski, Kirk Brower, Marcin Wojnar
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76)...
December 15, 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27973928/tyrosine-and-tryptophan-hydroxylases-as-therapeutic-targets-in-human-disease
#7
Kai Waløen, Rune Kleppe, Aurora Martinez, Jan Haavik
The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine hydroxylase (TH), tryptophan hydroxylase 1 (TPH1), and tryptophan hydroxylase 2 (TPH2) catalyse the rate-limiting steps in the biosynthesis of these monoamines. Genetic variants of TH, TPH1, and TPH2 genes are associated with neuropsychiatric disorders. The interest in these enzymes as therapeutic targets is increasing as new roles of these monoamines have been discovered, not only in brain function and disease, but also in development, cardiovascular function, energy and bone homeostasis, gastrointestinal motility, hemostasis, and liver function...
December 26, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27926628/variants-of-tph2-interact-with-fast-visual-processing-as-assessed-by-metacontrast
#8
Margus Maksimov, Mariliis Vaht, Carolina Murd, Jaanus Harro, Talis Bachmann
Sensitivity to threatening or otherwise unpleasant visual stimuli has become a widely used measure of potential vulnerability/resilience. Basically, experiments using this strategy present brief stimuli, often followed by a mask, and individuals' sensitivity is measured. However, it has not been asked whether the individual differences in threat detection or adaptive resilience associated with genetic variability-related endophenotypes might be just a function of some basic visual functions involved in processing and reporting brief visual stimuli without any emotional content...
January 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/27896310/preservation-of-essential-odor-guided-behaviors-and-odor-based-reversal-learning-after-targeting-adult-brain-serotonin-synthesis
#9
Kaitlin S Carlson, Meredith S Whitney, Marie A Gadziola, Evan S Deneris, Daniel W Wesson
The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27869229/tetratricopeptide-repeat-domain-9a-modulates-anxiety-like-behavior-in-female-mice
#10
Lee Wei Lim, Smeeta Shrestha, Yu Zuan Or, Shawn Zheng Kai Tan, Hwa Hwa Chung, Yang Sun, Chew Leng Lim, Sharafuddin Khairuddin, Thomas Lufkin, Valerie Chun Ling Lin
Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A(-/-)) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A(-/-) mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A(-/-) mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A(+/+) mice...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#11
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27824354/serotonergic-modulation-of-waiting-impulsivity-is-mediated-by-the-impulsivity-phenotype-in-humans
#12
S Neufang, A Akhrif, C G Herrmann, C Drepper, G A Homola, J Nowak, J Waider, A G Schmitt, K-P Lesch, M Romanos
In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents...
November 8, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27807918/local-gyrification-index-in-patients-with-major-depressive-disorder-and-its-association-with-tryptophan-hydroxylase-2-tph2-polymorphism
#13
Kyu-Man Han, Eunsoo Won, June Kang, Aram Kim, Ho-Kyoung Yoon, Hun Soo Chang, Kyu Ri Son, Min-Soo Lee, Woo-Suk Tae, Byung-Joo Ham
The tryptophan hydroxylase-2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD...
November 3, 2016: Human Brain Mapping
https://www.readbyqxmd.com/read/27761358/stabilization-of-tryptophan-hydroxylase-2-by-l-phenylalanine-induced-dimerization
#14
Kasper D Tidemand, Hans E M Christensen, Niclas Hoeck, Pernille Harris, Jane Boesen, Günther H Peters
Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full-length TPH2 is poorly characterized due to low purification quantities caused by its inherent instability. Three truncated variants of human TPH2 (rch TPH2; regulatory and catalytic domain, NΔ47-rch TPH2; truncation of 47 residues in the N terminus of rch TPH2, and ch TPH2; catalytic domain) were expressed, purified, and examined for changes in transition temperature, inactivation rate, and oligomeric state...
October 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27699247/pka-regulatory-subunit-1a-inactivating-mutation-induces-serotonin-signaling-in-primary-pigmented-nodular-adrenal-disease
#15
Zakariae Bram, Estelle Louiset, Bruno Ragazzon, Sylvie Renouf, Julien Wils, Céline Duparc, Isabelle Boutelet, Marthe Rizk-Rabin, Rossella Libé, Jacques Young, Dennis Carson, Marie-Christine Vantyghem, Eva Szarek, Antoine Martinez, Constantine A Stratakis, Jérôme Bertherat, Hervé Lefebvre
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters...
September 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/27695066/a-novel-interaction-between-tryptophan-hydroxylase-2-tph2-gene-polymorphism-rs4570625-and-bdnf-val66met-predicts-a-high-risk-emotional-phenotype-in-healthy-subjects
#16
Maeson S Latsko, T Lee Gilman, Lindsey M Matt, K Maria Nylocks, Karin G Coifman, Aaron M Jasnow
Poor inhibitory processing of negative emotional content is central to many psychiatric disorders, including depression and anxiety. Moreover, increasing evidence suggests that core aspects of emotion-inhibitory processing are largely inherited and as such may represent a key intermediate or risk-related phenotype for common affective diseases (e.g., unipolar depressive, anxiety disorders). The current study employed a candidate-gene approach in order to most effectively examine this complex behavioral phenotype...
2016: PloS One
https://www.readbyqxmd.com/read/27660918/pharmacogenetic-study-focused-on-fluoxetine-pharmacodynamics-in-children-and-adolescent-patients-impact-of-the-serotonin-pathway
#17
Sergi Mas, Ana Blázquez, Natalia Rodríguez, Daniel Boloc, Amalia Lafuente, Joan A Arnaiz, Luisa Lázaro, Patricia Gassó
OBJECTIVE: Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics. PATIENTS AND METHODS: The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways...
November 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27536220/firing-properties-of-genetically-identified-dorsal-raphe-serotonergic-neurons-in-brain-slices
#18
Boris Mlinar, Alberto Montalbano, Lukasz Piszczek, Cornelius Gross, Renato Corradetti
Tonic spiking of serotonergic neurons establishes serotonin levels in the brain. Since the first observations, slow regular spiking has been considered as a defining feature of serotonergic neurons. Recent studies, however, have revealed the heterogeneity of serotonergic neurons at multiple levels, comprising their electrophysiological properties, suggesting the existence of functionally distinct cellular subpopulations. In order to examine in an unbiased manner whether serotonergic neurons of the dorsal raphe nucleus (DRN) are heterogeneous, we used a non-invasive loose-seal cell-attached method to record α1 adrenergic receptor-stimulated spiking of a large sample of neurons in brain slices obtained from transgenic mice lines that express fluorescent marker proteins under the control of serotonergic system-specific Tph2 and Pet-1 promoters...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27522569/a-comparison-of-biomarker-responses-in-juvenile-diploid-and-triploid-african-catfish-clarias-gariepinus-exposed-to-the-pesticide-butachlor
#19
Ali Karami, Dzolkhifli Omar, James M Lazorchak, Chee Kong Yap, Zailina Hashim, Simon C Courtenay
Influence of waterborne butachlor (BUC), a commonly used pesticide, on morphometric, biochemical, and molecular biomarkers was evaluated in juvenile, full sibling, diploid and triploid African catfish (Clarias gariepinus). Fish were exposed for 21 days to one of three concentrations of BUC [mean measured µg/L: 22, 44 or 60]. Unexposed (control) triploids were heavier and longer and had higher visceral-somatic index (VSI) than diploids. Also, they had lighter liver weight (HSI) and showed lower transcript levels of brain gonadotropin-releasing hormone (GnRH), aromatase (cyp191b) and fushi tarazu-factor (ftz-f1), and plasma testosterone levels than diploids...
August 11, 2016: Environmental Research
https://www.readbyqxmd.com/read/27521242/tph-2-polymorphisms-interact-with-early-life-stress-to-influence-response-to-treatment-with-antidepressant-drugs
#20
Zhi Xu, Gavin P Reynolds, Yonggui Yuan, Yanyan Shi, Mengjia Pu, Zhijun Zhang
BACKGROUND: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al...
November 2016: International Journal of Neuropsychopharmacology
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